IL-15 and IL-15RAPLHA sushi domain based immunocytokines

Patent metadata

Field	Value
Publication number	US-11273204-B2
Application number	US-201414910475-A
Country	US
Kind code	B2
Filing date	Aug 8, 2014
Priority date	Aug 8, 2013
Publication date	Mar 15, 2022
Grant date	Mar 15, 2022

Abstract

The present invention relates to an immunocytokine comprising (a) a conjugate, and (b) an immunomodulatory antibody or a fragment thereof directly or indirectly linked by covalence to said conjugate, wherein said conjugate comprises (i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof, and a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof; and uses thereof.

First claim

We claim:

1. An immunocytokine comprising of:
a polypeptide conjugate and an immunomodulatory antibody or an antigen binding fragment thereof, which are covalently linked as a fusion protein,
wherein said immunomodulatory antibody or antigen binding fragment thereof binds to a PD-1 receptor; and
wherein said polypeptide conjugate comprises:
(i) an interleukin 15 comprising a) the amino acid sequence of SEQ ID NO: 3, or b) a variant thereof of a) comprising at least one amino acid substitution selected from L45D, L45E, S51D, L52D, N72D, N72E, N72A, N72S, N72Y and N72P according to SEQ ID NO: 3, wherein the variant has the IL-15 activity;
(ii) an IL-15Rα fragment comprising the sushi domain and the hinge domain of an IL-15Ra, and comprising the amino acid sequence of SEQ ID NO: 12; and
(iii) a flexible peptide linker joining the IL-15Ra fragment and the IL-15 to form a fusion protein.

2. The immunocytokine of claim 1 , comprising, from N- to C-terminal, the immunomodulatory antibody or antigen binding fragment thereof, the IL-15Ra fragment, and the IL-15.

3. The immunocytokine of claim 1 , wherein the linker consists of 18-22 amino acids.

4. The immunocytokine of claim 1 , wherein the linker consists of 20 amino acids.

5. The immunocytokine of claim 1 , wherein the linker consists of the amino acid sequence of SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15.

6. The immunocytokine of claim 1 , wherein the polypeptide conjugate comprises the amino acid sequence of SEQ ID NO:18 or SEQ ID NO: 19.

7. A pharmaceutical composition comprising the immunocytokine of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Cytune Pharma
• Univ Paris Descartes
• Hopitaux Paris Assist Publique
• Univ Paris
• Assist Publique—Hopitaux De Paris
• Inst Nat Sante Rech Med

Inventors

• Gey Alain
• Tartour Eric
• Bechard David

Classifications

• C07K16/2818

  against CD28 or CD152 · CPC title

• C07K14/7155

  for interleukins [IL] · CPC title

• C07K14/5443 Primary

  IL-15 · CPC title

• A61K47/6813

  the drug being a peptidic cytokine, e.g. an interleukin or interferon · CPC title

• A61K38/2086 Primary

  IL-13 to IL-16 · CPC title